This proposal aims at the fast-track pharmaceutical development and clinical validation of two artesunate-based fixed dose combinations for the treatment of malaria, including the preparation of relevant registration files. The goal is to make these new combination drugs available for use as quality, safe, viable, adapted and affordable drugs in the endemic countries. This project contributes a missing link in promoting antimalarial policy changes towards combination therapy, and the successful implementation thereof. It builds upon the expertise of R&D centres in the EU and different regions in the world, which are being mobilised in an international effort to improve dramatically the available malaria treatment tools.
Clinical trials and therapeutic experience have indicated that combinations of antimalarial drugs with different mechanisms of action, including artemisinin derivatives, improve therapy by preventing resistance. The success of the deployment of such drug combinations depends upon the availability of affordable fixed-dose combinations, adapted to the conditions of use. The proposal aims at promoting a therapeutic antimalarial policy change and the successful implementation thereof, by completing the development of quality, effective, safe, adapted and affordable fixed dose combinations of artesunate+mefloquine and artesunate+amodiaquine respectively. This will include preparing registration files and making the combination drug products available in the endemic countries by means of an international co-operation involving experts and institutes of the concerned countries.
The work will include six different types of activities:
1) Pre-clinical pharmaceutical development of the two fixed dose combination products (artesunate+mefloquine and artesunate+amodiaquine) for the generation of the Chemistry, Manufacturing and Control Sections (CMC) for the registration file and manufacturing of clinical batches. This will involve analytical and pharmaceutical sciences contributions.
2) Pre-clinical biological development and assessment, including a safety section (acute and adapted chronic administration) and a ‘mechanism of action’ contribution. This will require the development of adapted bioanalytical methods and conducting toxicokinetics studies in two animal species.
3) Clinical confirmation trials with the new formulations complementing existing data. This will also include an investigation of the bioavailability of the new combination.
4) Compilation of a registration documentation file, which can be submitted in the various malaria endemic countries.
5) Coordination of the work performed in different countries and regions.
6) Involvement in reviews and case studies with experts and authorities of the countries in which the new formulation will be developed and registered.
Year 1: Definition of the new formulations and scale-up of production. Pre-clinical safety and pharmacological data. Bioavailability of new formulations.
Year 2: Start of clinical studies. Identification of a manufacturing site.
Year 3: Clinical validation data. Stability analysis and reports. Registration of the new formulations.
Fondation Médecins sans Frontières
Access to Essential Medicines
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